Cellular and Molecular Life Sciences CMLS

, Volume 62, Issue 14, pp 1621–1631 | Cite as

Dual modes of 5-(N-ethyl-N-isopropyl)amiloride modulation of apical dipeptide uptake in the human small intestinal epithelial cell line Caco-2

Research Article


Selective pharmacological Na+/H+ exchange (NHE) inhibitors were used to identify functional NHE isoforms in human small intestinal enterocytes (Caco-2) and to distinguish between direct and indirect effects on transport via the intestinal di/tripeptide transporter hPepT1. The relative potencies of these inhibitors to inhibit 22Na+ influx identifies NHE3 and NHE1 as the apical and basolateral NHE isoforms. The Na+-dependent (NHE3-sensitive) component of apical dipeptide ([14C] Gly-Sar) uptake was inhibited by the selective NHE inhibitors with the same order of potency observed for inhibition of apical 22Na+ uptake. However, 5-(N-ethyl-N-isopropyl) amiloride (EIPA) also reduced [14C]Gly-Sar uptake in the absence of Na+ and this inhibition was concentration and pH (maximal at pH 5.5) dependent. NHE3 inhibition by S1611 and S3226 modulates dipeptide uptake indirectly by reducing the transapical driving force (H+ electrochemical gradient). EIPA (at 100 μM) has similar effects, but at higher concentrations (>200 μM) also has direct inhibitory effects on hPepT1.

Key words.

H+-coupled transport dipeptide transport intestinal absorption PepT1 Na+/H+ exchange NHE3 EIPA amiloride 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Birkhäuser Verlag, Basel 2005

Authors and Affiliations

  1. 1.Institute for Cell & Molecular Biosciences, Faculty of Medical SciencesUniversity of Newcastle upon TyneNewcastle upon TyneUK

Personalised recommendations